Single-cell RNA sequencing and spatial transcriptomics of bladder Ewing sarcoma
Bladder Ewing sarcoma/primitive neuroectodermal tumor (bladder ES/PNET) is a rare and highly malignant tumor associated with a poor prognosis, yet its underlying mechanisms remain poorly understood. Here, we employed a combination of single-cell RNA sequencing (scRNA-seq), spatial transcriptomics (ST), and functional analyses to delve into the pathogenesis of bladder ES/PNET. The investigation revealed the presence of specialized types of epithelial cells (referred to as bladder ES-Epi) and mast cells (referred to as bladder ES-Mast) within bladder ES/PNET in comparison to urothelial carcinoma. Notably, TNFRSF12A exhibited significant upregulation in bladder ES/PNET. Furthermore, mast cells possessed the ability to activate epithelial cells through the TNFSF12-TNFRSF12A ligand-receptor signaling pattern. In addition, Enavatuzumab can significantly inhibit the migratory ability of the Ewing sarcoma cell line RD-ES. This groundbreaking study provides unprecedented mechanistic insights into the progression of bladder ES/PNET and introduces a potential therapeutic avenue for treating this challenging malignancy.
Authors
- Weipu Mao
- Jiang Geng (ORCID: https://orcid.org/0000-0002-7202-2167)
- Chao Sun (ORCID: https://orcid.org/0000-0002-4585-3344)
- Atrayee Bhattacharya (ORCID: https://orcid.org/0000-0002-3322-6175)
- Houliang Zhang (ORCID: https://orcid.org/0000-0002-9283-1295)
- Kangjie Xu (ORCID: https://orcid.org/0000-0001-6885-3809)
- Jie Ji (ORCID: https://orcid.org/0000-0003-3792-5755)
- Tao Tao (ORCID: https://orcid.org/0000-0002-5009-8056)
- Ming Chen (ORCID: https://orcid.org/0000-0002-3572-6886)
- Jian Wu (ORCID: https://orcid.org/0000-0002-3394-1507)
- Fang Cheng (ORCID: https://orcid.org/0000-0001-9083-5826)
- Keyi Wang (ORCID: https://orcid.org/0000-0003-4234-8737)
- Chaoming Gu
- Shuqiu Chen (ORCID: https://orcid.org/0000-0003-4117-1917)
- Si Sun
- Bin Xu (ORCID: https://orcid.org/0009-0003-9487-9414)
Institutions
- Tongji University (CN)
- University of Science and Technology of China (CN)
- Harvard University (US)
- Zhongda Hospital Southeast University (CN)
- Dana-Farber Cancer Institute (US)
- Binzhou People's Hospital (CN)
- Shanghai Tenth People's Hospital (CN)
Publication Details
- Journal
- iScience
- Published
- 2024-09-12
- DOI
- https://doi.org/10.1016/j.isci.2024.110921
- Citations
- 4
- Primary Topic
- Single-cell and spatial transcriptomics
- Type
- article
- Field-Weighted Citation Impact
- 0.94
Funders
- National Natural Science Foundation of China
- Government of Jiangsu Province
- Natural Science Foundation of Jiangsu Province
- Southeast University